X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by pathogenic variants in the BTK gene, resulting in impaired B cell differentiation and maturation. Over 900 variants have already been described in this gene, however, new pathogenic variants continue to be identified. In this report, we describe 22 novel variants in BTK, associated with B cell deficiency with hypo- or agammaglobulinemia in male patients or in asymptomatic female carriers. Genetic data was correlated with BTK protein expression by flow cytometry, and clinical and family history to obtain a comprehensive assessment of the clinico-pathologic significance of these new variants in the BTK gene. For one novel missense variant, p.Cys502Tyr, site-directed mutagenesis was performed to determine the impact of the sequence change on protein expression and stability. Genetic data should be correlated with protein and/or clinical and immunological data, whenever possible, to determine the clinical significance of the gene sequence alteration.

X连锁无丙种球蛋白血症（XLA）是由BTK基因致病变异引起的先天免疫缺陷，导致B细胞分化和成熟受损。已经在该基因中描述了 900 多种变异，但是，仍在不断发现新的致病变异。在本报告中，我们描述了BTK中的 22 个新变体，这些变体与男性患者或无症状女性携带者的 B 细胞缺乏和低丙种球蛋白血症或丙种球蛋白缺乏症有关。通过流式细胞术将遗传数据与 BTK 蛋白表达、临床和家族史相关联，以获得对BTK中这些新变体的临床病理学意义的综合评估基因。对于一种新的错义变体 p.Cys502Tyr，进行定点诱变以确定序列变化对蛋白质表达和稳定性的影响。基因数据应尽可能与蛋白质和/或临床和免疫学数据相关联，以确定基因序列改变的临床意义。